Research in colorectal and pancreas cancer is proposed. It takes as its theme the following model: the interaction of cells with DNA damaging agents can result in three classes of cells-normal cells with intact DNA; cells with damaged DNA that undergo apoptosis; and cells which, despite DNA damage, fail to suicide. We propose to explore aspects of the differences in these three classes of cells to increase our understanding of the carcinogenesis process, to monitor interventions, identify markers that may be used for population screening, and to exploit for therapeutic purposes. Project 1 focuses on oxidative damage and apoptosis among a high-risk human populations- with pancreatitis- and an animal model in order to establish the roles of oxidative DNA damage and antioxidants in pancreatitis and pancreas cancer, and to develop a clinical screening test. Project 2 also focuses on a high-risk inflammatory disease- ulcerative colitis-in order to determine the role of DNA damage and mutagenesis in the progression of UC dysplasia. In addition, an intervention with antioxidants is proposed to reverse of slow the dysplasia neoplasia sequence. Project 3 focuses on colonoscopy patients with the specific aim of identifying several processes in the pathways to neoplasia, including oxidative damage and changes in expression of apoptosis-related proteins, that will allow the early identification of high-risk individuals in a low-cost, minimally invasive manner.